Metabolic isotopomer labeling systems. Part I: global dynamic behavior.

In the last few years metabolic flux analysis (MFA) using carbon labeling experiments (CLE) has become a major diagnostic tool in metabolic engineering. The mathematical centerpiece of MFA is the solution of isotopomer labeling systems (ILS). An ILS is a high-dimensional nonlinear differential equation system that describes the distribution of isotopomers over a metabolic network during a carbon labeling experiment. This contribution presents a global analysis of the dynamic behavior of general ILSs. It is proven that an ILS is globally stable under very weak conditions that are always satisfied in practice. In particular it is shown that in some sense ILSs are a nonlinear extension to the classical theory of compartmental systems. The central stability condition for compartmental systems, i.e., the non-existence of traps in linear compartmental networks, is also the major stability condition for ILSs. As an important side result of the proof, it is shown that ILSs can be transformed to a cascade of linear systems with time-dependent inhomogeneous terms. This cascade structure has considerable consequences for the development of efficient numerical algorithms for the solution of ILSs and thus for MFA.

Constrictive pericarditis. Early experience in 12 patients in light of modern cardiology.

The last several decades have witnessed major advances in the understanding and management of constrictive pericarditis. The aim of the present study was to compare the diagnosis, treatment and outcome of constrictive pericarditis of 40 years ago to today. The study population consisted of 12 patients with a diagnosis of constrictive pericarditis who presented at the Institute of Cardiology of Beilinson Hospital, from 1961 to 1970. Their main physical findings, electrocardiographic and chest X-ray changes, and hemodynamic study results are discussed in relation to the surgical outcome of patients with constrictive pericarditis today. New noninvasive imaging modalities, such as M mode, two-dimensional and Doppler echocardiography, computed tomography and magnetic resonance imaging are presented, and their advantages and disadvantages in the diagnosis of constrictive pericarditis and its differentiation from restrictive cardiomyopathy are explained.

Bidirectional reaction steps in metabolic networks: III. Explicit solution and analysis of isotopomer labeling systems.

The last few years have brought tremendous progress in experimental methods for metabolic flux determination by carbon-labeling experiments. A significant enlargement of the available measurement data set has been achieved, especially when isotopomer fractions within intracellular metabolite pools are quantitated. This information can be used to improve the statistical quality of flux estimates. Furthermore, several assumptions on bidirectional intracellular reaction steps that were hitherto indispensable may now become obsolete. To make full use of the complete measurement information a general mathematical model for isotopomer systems is established in this contribution. Then, by introducing the important new concept of cumomers and cumomer fractions, it is shown that the arising nonlinear isotopomer balance equations can be solved analytically in all cases. In particular, the solution of the metabolite flux balances and the positional carbon-labeling balances presented in part I of this series turn out to be just the first two steps of the general solution procedure for isotopomer balances. A detailed analysis of the isotopomer network structure then opens up new insights into the intrinsic structure of isotopomer systems. In particular, it turns out that isotopomer systems are not as complex as they appear at first glance. This enables some far-reaching conclusions to be drawn on the information potential of isotopomer experiments with respect to flux identification. Finally, some illustrative examples are examined to show that an information increase is not guaranteed when isotopomer measurements are used in addition to positional enrichment data.

Tricuspid regurgitation late after mitral valve replacement: clinical and echocardiographic evaluation.

BACKGROUND AND AIM OF THE STUDY: Significant tricuspid regurgitation (TR) can contribute to increased morbidity and mortality in patients after mitral valve replacement (MVR), both in the immediate and late postoperative period. The aim of this study was to evaluate the prevalence and the clinical importance of TR late after MVR, as assessed both clinically and echocardiographically. METHODS: The study group comprised 65 patients (39 women, 26 men; mean age 61+/-12 years) with rheumatic heart disease who had undergone MVR without tricuspid valve surgery between one and 30 years (mean 11.3+/-8 years) before their last clinical examination. All patients underwent a complete color-Doppler echocardiographic examination. The predominant presurgical mitral lesion was stenosis in 44 patients and regurgitation in 21. The severity of the tricuspid valve disease was assessed echocardiographically using color-Doppler flow images and flow direction in the inferior vena cava or hepatic veins, and by clinical evaluation. RESULTS: Echocardiography revealed significant late TR in 44 patients (67%), which was moderate in 16 and severe in 28, and evident on physical examination in 24 cases (37%). Age (relative risk (RR) = 1.1; C.I. 1-1.1) and female sex (RR = 1.8; C.I. = 1.0-3.2) were identified as statistically significant predictors for late clinical TR development, but only age was found as a statistically significant predictor for echocardiographic TR development. An elevated RR for organic TR and predominant mitral regurgitation was found. In contrast, pre- and postoperative pulmonary artery pressure, predominant mitral lesion, prosthetic valve gradient and regurgitation were similar in patients with and without late TR. CONCLUSIONS: Significant TR diagnosed by echocardiography late after MVR is common, and clinically evident in more than one-third of patients. Therefore, a lower threshold for tricuspid valve repair should be considered when mitral valve surgery is carried out.

Evaluation of tricuspid regurgitation severity: echocardiographic and clinical correlation.

The correlation between 19 echocardiographic markers of tricuspid regurgitation (TR) severity and findings on physical examination was studied in 66 consecutive patients (age 63 +/- 12 years) with moderate or severe TR. Clinical TR was defined by two or more of the following: prominent jugular venous pulse V waves, pulsating liver, and sea-saw parasternal movement. Thirty-eight patients (57.6%) had clinical TR, whereas 28 patients (42.4%) did not. In a univariate analysis, the most powerful predictors of clinical TR (p < 0.01) were jet area > or =9 cm2, right atrial area > or =30 cm2, jet width at origin > or =0.8 cm, systolic flow reversal in the hepatic veins, paradoxical septal movement, diastolic septal flattening, inferior vena cava diameter > or =2.1 cm, and lack of inferior vena cava respiratory variation. Regurgitant index was a weaker predictor. Multivariate analysis showed that the only independent echocardiographic predictor of clinical TR was systolic flow reversal (positive and negative predictive values 91.2% and 78.1%, respectively). Significant echocardiographic TR can be subclinical in a substantial number of patients.

Long-term prognosis of 210 patients who underwent coronary angiography before 40 years of age.

We report on a follow-up of 210 patients who underwent coronary angiography before age 40. We found that young patients with normal coronary arteries have an excellent prognosis, whereas those with single-vessel disease have an unfavorable outcome resembling that of patients with multivessel disease.

Abnormal diastolic unopacified blood front: a useful marker of mitral stenosis.

The left ventriculograms of 113 patients, divided into seven groups, were reviewed for the detection of unopacified front (UOF) of blood entering the left ventricle (LV) during diastole. Normal UOF was detected in all the patients without left-sided valvular heart disease (regardless of the existence of coronary artery disease), constrictive pericarditis, aortic stenosis, and mitral regurgitation, although in the last group the UOF faded after several beats in 70% of cases. Only 5% of the patients with isolated mitral stenosis (MS) had an UOF, 75% had an abnormal UOF (< 60% of LV inflow tract), and 20% (with the greatest degree of MS) had only a dilution effect. A dilution effect was found in 62.5% of the patients with severe (> or = 3 degrees) aortic regurgitation (AR). An abnormal UOF is a sensitive and specific marker of significant MS. A dilution effect is indicative of either a significant MS or severe AR.

Systolic rightward displacement of the left anterior descending artery: a novel cineangiographic sign for tricuspid regurgitation.

A new sign for the detection of tricuspid regurgitation (TR) is described. The systolic displacement of the left anterior descending (LAD) artery during coronary angiography in left anterior oblique (LAO) view was quantitatively calculated in 3 groups of 20 patients each with either TR, mitral stenosis, or normal coronary arteriograms. The mean LAD displacement in the TR group was significantly rightward compared to the other groups. Uniform rightward displacement of the lower two-thirds of the LAD had a 90% sensitivity and 90-95% specificity for the presence of TR. Such displacement is probably the angiographic counterpart of the systolic paradoxical septal displacement demonstrated by echocardiography in patients with right ventricular volume overload. There was a positive correlation between the severity of TR and the magnitude of LAD displacement. Attention to the LAD displacement on LAO view may raise suspicion of TR, and indicate its severity.

The effect of lovastatin on early restenosis.

The effect of lovastatin given before percutaneous coronary angioplasty (PTCA) on early restenosis was investigated in men with mild to moderate hypercholesterolemia. Thirty-four hypercholesterolemic patients (serum LDL cholesterol 130-200 mg/dL) undergoing their first PTCA completed a 6-month prospective, double-blind, placebo-controlled trial. Eighteen received lovastatin 20 mg/day (Lo group) and 16 placebo (P1 group), beginning 10 to 21 days before PTCA. All underwent a thallium-201 quantitative exercise test 5 to 7 days after PTCA. Endpoints for restenosis were either 50% narrowing of the dilated artery on coronary angiography, performed in symptomatic patients or, in asymptomatic patients, the appearance of newly developed reversible filling defects in the vascular territory of the dilated artery on a second thallium scan done 6 months after PTCA. The hypocholesterolemic change observed in the Lo group was not accompanied by a reduction in early restenosis risk. The authors conclude that effective hypocholesterolemic therapy before PTCA does not affect early restenosis rate in men with mild to moderate hypercholesterolemia.

Isolated mid-anterior myocardial infarction: a special electrocardiographic sub-type of acute myocardial infarction consisting of ST-elevation in non-consecutive leads and two different morphologic types of ST-depression.

UNLABELLED: We describe eight patients with a distinct electrocardiographic pattern of anterior wall myocardial infarction characterized by three main features: (1) a pattern of 'transmural ischemia' (ST-elevation with positive T-wave) in non-consecutive leads: a VL and V2, and two different types of ST-depression; (2) a pattern of 'true reciprocal changes' (ST-depression and negative T-wave) in III and a VF; (3) a pattern of 'sub-endocardial ischemia' (ST-depression with positive T-wave) in V4-5, while ST in V3 was either isoelectric or depressed. We characterize the electrocardiographic features and correlate them with the echocardiographic, radionuclide, and angiographic data. All patients admitted to the coronary care unit from January 1990 to April 1992 with evolving acute myocardial infarction were evaluated prospectively. Patients whose admission electrocardiogram met the description above were included. The electrocardiographic evolution, echocardiographic, Technetium MIBI tomography, and coronary angiography are described. Of 471 patients with acute anterior wall myocardial infarction, admitted to the coronary care unit during the study period, eight patients met the inclusion criteria (1.7% of acute anterior wall myocardial infarction). Echocardiographic studies revealed mid-anterior hypokinesis in two patients, anterior and apical hypokinesis in one, and no wall motion abnormality in four patients. Technetium MIBI tomography, done in five patients, was consistent with mid-anterior or midanterolateral infarction without involvement of the septum or apex. Coronary angiography, performed in seven patients, demonstrated significant obstruction of the first diagonal branch in all of the patients. In four patients, the diagonal occlusion was the only significant coronary lesion in the left coronary artery. CONCLUSION: Most of the anterior myocardial infarctions also involve the septal and apical regions. Anterior wall myocardial infarctions limited to the mid-anterior or mid-anterolateral wall, without apical or septal wall involvement are relatively rare. This study describes a special electrocardiographic form of anterior wall acute myocardial infarction. This distinct electrocardiographic pattern represents true mid-anterior wall myocardial infarction, caused by occlusion of a first diagonal branch of the left anterior descending coronary artery. The septal and apical regions are not involved because the blood supply via the left anterior descending artery is not interrupted.

An unusual cause of recurrent angina two years after coronary artery bypass grafting: fistula between internal mammary artery graft to pulmonary vasculature.

A 55-year-old man developed recurrent angina pectoris 2 years after coronary artery bypass grafting. Cardiac catheterization demonstrated that the venous grafts were patent, but selective left internal mammary angiogram showed multiple fistulous connections between the internal mammary artery and the pulmonary vasculature of the left upper lobe. After surgical correction of the fistula, the angina resolved. Only three previous cases of acquired internal mammary artery graft fistulas draining to the pulmonary vasculature have been described. The etiology, clinical presentation, and management of an internal mammary artery fistula to the pulmonary vasculature are discussed.

Segmental early relaxation of the left ventricle.

The clinical, electrocardiographic, and angiographic findings of 90 patients, whose RAO 30 degrees left ventriculograms showed segmental early relaxation (SER), were compared with those of 100 patients without SER. There were no significant differences in age and sex distribution or in clinical and coronary angiographic findings between the two groups. There was, however, a significantly lower prevalence of pathologic Q or QS patterns in the anterior leads of the ECG in the group with SER. SER occurred more frequently in segments with well-preserved systolic contraction and was confined to the anterolateral segments in the great majority of the patients (80%). An inverse correlation was found between SER and geographically related critical coronary artery stenosis.

Unusual electrocardiogram in hypertrophic cardiomyopathy.

Electrocardiographic criteria of right ventricular hypertrophy were found in a 17-year-old male with nonobstructive hypertrophic cardiomyopathy involving the left ventricle. Right ventricular hypertrophy pattern is a rare electrocardiographic abnormality in patients with hypertrophic cardiomyopathy and the presence of Q waves in leads V5-V6 could be helpful in differentiating this syndrome from true right ventricular hypertrophy.

Anomalous origin of the coronary arteries.

The incidence and the clinical significance of various forms of anomalous aortic origin of coronary arteries are not well known. Among 2,000 consecutive patients who underwent selective coronary aretriography, 11 had such anomalies (0.55%). Two patients with atresia of the left main ostia developed ischemic symptoms at the ages of thirty-five and fifty-two, and both benefitted from coronary bypass graft operation. In other forms of anomalies the presence of ischemic symptoms was also associated with atherosclerotic stenosis (7 patients) or with constricting muscle bridge (1 patient).

Positivization of T wave with or without ST segment elevation in patients with unstable angina. Coronary angiographic findings and in-hospital prognosis.

The coronary angiographic findings and the in-hospital prognosis of unstable angina pectoris presenting with T wave positivization only (group A: 32 patients) or with additional ST segment elevation (group B: 27 patients) were evaluated. Clinical data and haemodynamic parameters before and during unstable anginal events showed no significant statistical difference, indicating blood flow reduction as the probable mechanism of ischaemia in both groups. The incidence of hospital myocardial infarction was higher in patients of group B (group A 6.24% vs group B 31%; P less than 0.02). Death due to haemodynamic deterioration occurred in 2 patients of group B. This finding can be partially explained by more developed collateral circulation in patients with T wave changes only (25 of 65 obstructed arteries in group A vs 8 out of 48 obstructed arteries in group B; P less than 0.05). Left ventricular function was comparable between the two groups. The extent, severity and location of coronary artery disease was similar in the groups. Thus, the electrocardiographic pattern of T wave changes only, in patients with unstable angina pectoris (group A) define a subgroup who have a favourable prognosis and development similar to patients with chronic stable angina pectoris. Urgent measures may be delayed in this group.

Unusual electrocardiographic presentation of idiopathic hypertrophic subaortic stenosis.

A patient with idiopathic hypertrophic subaortic stenosis and normal coronary arteries, with dynamic electrocardiographic changes resembling acute myocardial ischemia, is presented. A definite association between the electrocardiographic changes and the idiopathic hypertrophic subaortic stenosis cannot be absolutely confirmed; however, the findings demonstrate the broad spectrum of electrocardiographic presentation in this disease.